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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 7 December 2020
Main ID:  EUCTR2019-003076-39-NL
Date of registration: 25/03/2020
Prospective Registration: Yes
Primary sponsor: argenx BVBA
Public title: A study to assess the safety and efficacy of a subcutaneous formulation of efgartigimod in adults with chronic inflammatory demyelinating polyneuropathy (an autoimmune disorder that affects the peripheral nerves)
Scientific title: A Phase 2 Trial to Investigate the Efficacy, Safety, and Tolerability of Efgartigimod PH20 SC in Adult Patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) - ADHERE
Date of first enrolment: 03/07/2020
Target sample size: 400
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-003076-39
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
Number of treatment arms in the trial: 2
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Belgium Bulgaria Canada Czechia Denmark France Georgia Germany
Hungary Israel Italy Japan Latvia Netherlands Poland Romania
Russian Federation Serbia Spain Ukraine United Kingdom United States
Contacts
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7 B-9052 Zwijnaarde Belgium
Telephone: 00329 310 3400
Email: regulatory@argenx.com
Affiliation:  argenx BVBA
Name: Regulatory   
Address:  Industriepark Zwijnaarde 7 B-9052 Zwijnaarde Belgium
Telephone: 00329 310 3400
Email: regulatory@argenx.com
Affiliation:  argenx BVBA
Key inclusion & exclusion criteria
Inclusion criteria:
Patients are eligible to be included in the trial only if all of the following criteria apply:
1. Ability to understand the requirements of the trial, provide written informed consent (include consent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including required trial visits)

2. Male or female patient aged 18 years or older, at the time of signing the informed consent.

3. Diagnosed with probable or definite CIDP according to criteria of the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS 2010), progressing or relapsing forms.

4. CIDP Disease Activity Status (CDAS) score =2 at screening

5. INCAT score =2, with a score of 2 exclusively from leg disability,at the first run-in visit (RI-VI; for patients entering run-in) or stage A baseline (A-VI; for treatment-naïve patients with documented evidence for worsening on the total adjusted INCAT disability score within 3 months prior to screening)

6. Fulfilling any of the following treatment conditions:
-Currently treated with pulsed corticosteroids, oral corticosteroids equivalent to prednisolone/prednisone =10mg/day, and/or IVIg or SCIg, if this treatment has been started within the last 5 years before screening, and the patient is willing to discontinue this treatment at the first run-in visit (RI-VI); or
-Without previous treatment (treatment-naive); or
-Treatment with corticosteroids and/or IVIg or SCIg discontinued at least 6 months prior to screening
Note: Patients not treated with monthly or daily corticosteroids, IVIg or SCIg for at least 6 months prior to screening are considered as equal to treatment-naïve patients.

7. Women of childbearing potential who have a negative pregnancy test at screening and a negative urine pregnancy test up to Stage A baseline (D1A).

8. Women of childbearing potential must use a highly effective method of contraception (failure rate of less than 1% per year) from screening to 90 days after the last administration of IMP

9. Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom and his partner must use a highly effective method of contraception (failure rate of less than 1% per year) from screening to 90 days after the last administration of IMP . Male patients practicing true sexual abstinence (when this is in line with the preferred and usual life style of the participant) can be included. Sterilized male patients who have had vasectomy with documented aspermia post-procedure can be included. In addition, male patients are not allowed to donate sperm from screening to 90 days after the last administration of IMP
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160

Exclusion criteria:
Patients are excluded from the trial if any of the following criteria apply:
1. Pure sensory atypical CIDP (EFNS/PNS definition(11)).
2. Polyneuropathy of other causes, including the following:
-Multifocal motor neuropathy;
-Monoclonal gammopathy of uncertain significance with anti-myelin-associated glycoprotein immunoglobulin M (IgM) antibodies;
-Hereditary demyelinating neuropathy;
-Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin change syndromes;
-Lumbosacral radiculoplexus neuropathy;
-Polyneuropathy most likely due to diabetes mellitus;
-Polyneuropathy most likely due to systemic illnesses;
-Drug- or toxin-induced polyneuropathy.

3. Any other disease that could better explain the patient’s signs and symptoms.

4. Any history of myelopathy or evidence of central demyelination.

5. Current or past history (within 12 months of screening) of alcohol, drug or medication abuse.

6. Severe psychiatric disorder (such as severe depression, psychosis, bipolar disorder), history of suicide attempt, or current suicidal ideation that in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol.

7. Patients with clinically significant active or chronic uncontrolled bacterial, viral, or fungal infection at screening, including patients who test positive for an active viral infection at screening with:
- Active Hepatitis B Virus (HBV): serologic panel test results indicative of an active (acute or chronic) infection;
- Active Hepatitis C Virus (HCV): serology positive for HCV-Ab;
- Human Immunodeficiency Virus (HIV) positive serology associated with an Acquired Immune Deficiency Syndrome (AIDS)-defining condition or with a cluster of differentiation 4 (CD4) count =200 cells/mm3.

8. Total IgG level <6 g/L at screening.

9. Treatment with the following:
-Within 3 months (or 5 half-lives of the drug, whichever is longer) before screening: plasma exchange or immunoadsorption, any concomitant Fc-containing therapeutic agents or other biological, or any other investigational product;
-Within 6 months before screening: rituximab, alemtuzumab, any other monoclonal antibody, cyclophosphamide, interferon, tumor necrosis factor–alpha inhibitors, fingolimod, methotrexate, azathioprine, mycophenolate, any other immunomodulating or immunosuppressive medications, and oral daily corticosteroids >10 mg/day.
Note: Patients using IVIg, SCIg, pulsed corticosteroids, and oral daily corticosteroids =10 mg/day can be included.

10. Pregnant and lactating women and those intending to become pregnant during the trial or within 90 days after last IMP administration.

11. Patients with any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of CIDP.

12. Use of an investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) prior to first IMP administration.

13. Patients who have a history of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for =3 years before the first IMP administration. Patients with the following cancer can be included anytime:
-Adequately treated basal cell or squamous cell skin cancer,
-Carcinoma in situ of the cervix,
-Carcinoma in situ of the breast, or
-Incidental histological finding of Prostate cancer (TNM [tumor, nodes, and metastases classification] stage T1a or T1b)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Chronic Inflammatory Demyelinating Polyneuropathy
MedDRA version: 20.0 Level: LLT Classification code 10077384 Term: Chronic inflammatory demyelinating polyneuropathy System Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Intervention(s)

Product Name: Efgartigimod PH20 SC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Efgartigimod alfa
CAS Number: 1821402-21-4
Current Sponsor code: ARGX-113
Other descriptive name: ARGX-113
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 165-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)
Main Objective: Stage A: To assess the activity of efgartigimod PH20 SC based on the percentage of patients classified as treatment responders.

Stage B: To determine the efficacy of efgartigimod PH20 SC compared to placebo based on the time needed for the occurrence of the first evidence of clinical deterioration.
Primary end point(s): Stage A
Percentage of patients with confirmed evidence of clinical improvement (ECI).

Stage B
Stage B: Time to first adjusted INCAT deterioration compared to Stage B baseline

Secondary Objective: Stage A
- To assess the time to clinical improvement.
-To determine the treatment effect of efgartigimod PH20 SC based on clinical functional assessments of motor function and muscle strength.
-To assess the short-term safety and tolerability of efgartigimod PH20 SC.
-To assess the pharmacokinetics (PK) of efgartigimod PH20 SC.
-To assess the pharmacodynamic (PD) effect of efgartigimod PH20 SC.
-To assess the immunogenicity of efgartigimod and rHuPH20.
Stage B
-To determine the efficacy of efgartigimod PH20 SC compared to placebo based on clinical functional assessments of disease disability and motor function and muscle strength.
-To assess the safety and tolerability of efgartigimod PH20 SC.
-To assess the PK of efgartigimod PH20 SC.
-To assess the PD effect of efgartigimod PH20 SC.
-To assess the immunogenicity of efgartigimod and rHuPH20.
Timepoint(s) of evaluation of this end point: Stage A
Up to 12 weeks (with option 1 additional week for confirmation of ECI) during the open-label stage A

Stage B
Every Stage B visit
Secondary Outcome(s)
Secondary end point(s): Stage A
- Time to initial confirmed ECI
- Change from Stage A baseline (D1A) over time in adjusted INCAT score
- Change from Stage A baseline (D1A) over time in Medical Research Council (MRC) Sum score
- Change from Stage A baseline (D1A) over time in 24-item Inflammatory Rasch-built Overall Disability Scale (I-RODS) disability scores
- Change from Stage A baseline (D1A) over time in Timed Up-and-go (TUG) score
- Change from Stage A baseline (D1A) over time in Mean grip strength
- Exposure adjusted occurrence of treatment-emergent adverse events and serious adverse events
- Incidence of clinically significant laboratory abnormalities
- Pre-dosing efgartigimod serum concentrations over time
- Changes of serum IgG levels (total and IgG subtypes) over time
- Percentage of patients with and titers of binding antibodies towards efgartigimod and/or rHuPH20 and the presence of neutralizing antibodies against efgartigimod and/or rHuPH20


Stage B
- Time to CIDP disease progression.
Note: Time to CIDP disease progression is defined by the time from first dose of double-blind IMP to the first I-RODS score decrease =4 points compared to Stage B baseline using the centile metric.
- Percentage of patients with improved functional level compared to Stage B baseline as measured by an increase in the 24-item I-RODS score up to Week 48
- Change from Stage B baseline over time in adjusted INCAT score
- Change from Stage B baseline over time in MRC Sum score
- Change from Stage B baseline over time in 24-item I-RODS disability score
- Change from Stage B baseline over time in TUG score
- Change from Stage B baseline over time in mean grip strength
- Time to 10% decrease in the 24-item I-RODS
- Exposure adjusted occurrence of treatment-emergent adverse events and serious adverse events
- Incidence of clinically significant laboratory abnormalities
- Pre-dosing efgartigimod serum concentrations over time
- Changes of serum IgG levels (total and IgG subtypes) over time
- Percentage of patients with and titers of binding antibodies towards efgartigimod and/or rHuPH20 and the presence of neutralizing antibodies against efgartigimod and/or rHuPH20
Timepoint(s) of evaluation of this end point: Stage A
Up to 12 weeks (with option 1 additional week for confirmation of ECI) during the open-label stage A

Stage B
Up to 48 weeks during the randomized placebo-controlled stage B
Secondary ID(s)
2019-003076-39-DE
ARGX-113-1802
Source(s) of Monetary Support
argenx BVBA
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 03/07/2020
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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